Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregn...Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites.In species with invasive hemochorial placentation,these uterine natural killer(uNK)cells,via secretion of cytokines,chemokines,mucins,enzymes and angiogenic growth factors,contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis.In humans,uNK cells have the phenotype CD56^(bright) CD16^(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy.Gene expression studies indicate that CD56^(bright) CD16^(dim) uterine and circulating cells are functionally distinct.In humans but not mice or other species with post-implantation decidualization,uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility.Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function,achieved via interferon(IFN)-c secretion.During spiral arterial modification,branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict.The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance,high-volume channels.Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women.Here we briefly review key information concerning uNK cell functions from studies in rodents,summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized,pregnant mouse model for in vivo investigations of human 展开更多
During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system i...During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells （NKs）, macrophages, T cells and dendritic cells （DCs） altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56brightCD16 phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy. However, there is a tendency for pregnancy immunology to reflect transplantation immunology regarding the assumption that the matemal immune system should be suppressed. This tendency is misleading. We discuss how the immune system is formed in early deciduas and the interactions between maternal NK cells and fetal growth. We propose that the maternal immune response must not be fully suppressed and is even necessary for the local response of uterine NK cells.展开更多
基金These studies were supported by awards from the Natural Sciences and Engineering Research Council,Canada,the Canadian Institutes of Health Research and the Canada Research Chairs Program to BAC and a Province of Ontario/Queen’s Postdoctoral Fellowship award to JHZ.
文摘Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites.In species with invasive hemochorial placentation,these uterine natural killer(uNK)cells,via secretion of cytokines,chemokines,mucins,enzymes and angiogenic growth factors,contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis.In humans,uNK cells have the phenotype CD56^(bright) CD16^(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy.Gene expression studies indicate that CD56^(bright) CD16^(dim) uterine and circulating cells are functionally distinct.In humans but not mice or other species with post-implantation decidualization,uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility.Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function,achieved via interferon(IFN)-c secretion.During spiral arterial modification,branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict.The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance,high-volume channels.Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women.Here we briefly review key information concerning uNK cell functions from studies in rodents,summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized,pregnant mouse model for in vivo investigations of human
基金supported by the Natural Science Foundation of China(91442202,81330071,81471527)
文摘During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells （NKs）, macrophages, T cells and dendritic cells （DCs） altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56brightCD16 phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy. However, there is a tendency for pregnancy immunology to reflect transplantation immunology regarding the assumption that the matemal immune system should be suppressed. This tendency is misleading. We discuss how the immune system is formed in early deciduas and the interactions between maternal NK cells and fetal growth. We propose that the maternal immune response must not be fully suppressed and is even necessary for the local response of uterine NK cells.
